Objective To investigate the protective effects of imipramine on alveolar epithelial barrier functiou in mice against LPS-induced acute lung injury (ALI),and explore the possible mechanisms.Methods Total of 32 SPF male Balb/c mice were randomly (random number) divided into four groups:control group,Imipramine group,LPS group,LPS + Imipramine group.To establish an animal model of ALI,mice were administered intraperitoneally with LPS in 20 mg/kg.Mice were treated with imipramine in 25 mg/kg 30 min prior to LPS administration.FITC-FD4 was administered in mice via the tail vein with FITC-FD4 10 min before mice sacrificed under anesthesia at 12 hours after LPS administration,then bronchoalveolar lavage fluid (BALF) and lung tissue were obtained.HE staining was used to observe histopathological changes,and pathology scores;lung tissue wet-to-dry weight ratio and BALF/serum FD4 ratio were used to assess pulmonary edema and alveolar epithelial permeability.Real-time PCR,western blot and immunochemistry were employed to detect the mRNA expressions and protein levels of Occludin,Claudin-4 and ZO-1.Data were analyzed with SPSS 16.0 software,one way analysis of variance (ANOVA) was used to compare multiple sets of variables,the intergroup comparisons were analyzed by the least-significant-difference (LSD) tests with P ＜ 0.05 for the statistically significant difference.Results Compared with LPS group,LPS + lmipramine group had a statistically significant decrease in pathological score [(9.22 ± 0.21) vs.(11.23 ± O.55),P ＜ O.05);the wet-to-dry weight ratio in LPS + Imipramine group was less than that in LPS group and the difference was statistically significant (P ＜ 0.05);compared with LPS group,the ratio of BALF/serum FD4 in LPS + Imipramine was less and the difference was statistically significant (P ＜ 0.05);compared with LPS group,the mRNA expressions and protein levels of Occludin,Claudin-4 and ZO-1 in LPS + Imipramine group were significantly increased (mRNA:Occludin:P ＜ 0.05;Claudin-4:P ＜ 0.05;ZO-1:P ＜ 0.05 . western blot:Occludin:P ＜ 0.05;Claudin-4:P ＜ 0.05;ZO-1:P ＜ 0.05).Immunochemistry showed that Occludin and Claudin-4 were present mainly in alveolar epithelial cell membrane,Z0-1 was found mainly in cytoplasm of alveolar epithelial cell.In control group and Imipramine group,tight junction proteins were obviously expressed.Compared with control group,protein levels in LPS group were significantly decreased (Occludin:P ＜ 0.05;Claudin-4:P ＜ 0.05;ZO-1:t =6.59,P ＜ 0.05);compared with LPS group,the tight junction proteins in LPS + Imipramine group were significantly increased (Occludin:P ＜ 0.05;Claudin-4:P ＜ 0.05;ZO-1:P ＜ 0.05).Conclusion The protective effects of imipramine on alveolar epithelial barrier function by up-regulating tight junction proteins expression in murine LPS-induced ALI.

OBJECTIVETo study the effects of four kinds of traditional Chinese herbal compound, Sini powder, Banxiahoupu soup, Ganmaidazao soup and Guizhigancaolonggumuli soup, on the experimental acute stress behaviors and the hypothalamus-pituitary-adrenal gland axis.

METHODRats were divide into 7 groups: normal group, model 1 and 2 groups, Sini powder group, Banxiahoupu soup group, Ganmaidazao soup group, and Guizhigancaolonggumuli soup group. The behaviors of the rats and their CRH of the hypothalamus, ACTH of plasma and CORT of serum (by the means of radio-immunity) were detected.

RESULTSini powder could reduce the crossing times of open-field test( P < 0.01) and the contents of CRH and CORT (P < 0.01, P < 0.05); Banxiahoupu soup could extent the still time of tail-hanging test ( P < 0.05) and the content of CRH (P < 0.05); Ganmaidazao soup could prolong the still time (P < 0.05) and reduce the struggle times (P < 0.01) of tail-hanging test and reduce the contents of CRH, ACTH and CORT (P < 0.01, P < 0.05); Guizhigancaolonggumuli soup could reduce the crossing times of open-field test (P < 0.01) , extent the still time (P < 0.05) and reduce the struggle times ( P < 0.01) of tail-hanging test of tail-hanging test, also reduce the contents of CRH, ACTH and CORT (P < 0.01, P < 0.05).

CONCLUSIONThe four kinds of traditional Chinese herbal compound can increase the ability of anti stress by affect the different taches of the hypothalamus-pituitary-adrenal gland axle and change the stress behaviors, which are based on their respective functions of regulating Qi, dispersing phlegm, tonifying Qi and warming Yang.

Adrenocorticotropic Hormone ; blood ; Animals ; Behavior, Animal ; drug effects ; Corticosterone ; blood ; Corticotropin-Releasing Hormone ; metabolism ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Female ; Hypothalamo-Hypophyseal System ; drug effects ; Hypothalamus ; metabolism ; Male ; Materia Medica ; isolation & purification ; pharmacology ; Medicine, Chinese Traditional ; Ostreidae ; chemistry ; Plants, Medicinal ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Stress, Physiological ; physiopathology

OBJECTIVETo study the effects of Erlong Zuoci Pill (, ELZCP) and its disassembled: prescriptions on gentamicin (GM)-induced ototoxicity model in vitro.

METHODSAfter the spiral organ of cochleae: of newborn mice (postnatal days: 2-3) cultured for 24 h, GM alone or combined with water extracting-alcohol precipitating solution of ELZCP or with its disassembled prescriptions was added. Hair cells were observed under a fluorescence microscope after TRITC-phalloidin staining, and the cochlear hair cell loss rate was calculated by counting the whole cochlear hair cells and analyzed by whole cochlear hair cells analyzing software.

RESULTSGM induced cochlear outer hair cells (OHCs) and inner hair cells (IHCs) injuries in a dose-dependent manner, and they were significantly different as compared with those in the normal control group (P<0.05, P<0.01). ELZCP at the concentration of 0.003-3 mg/mL could decrease the hair cells loss induced by the 0.3 mmol/L GM (P<0.05, P<0.01), the effects was in a dose-dependent manner, and the concentration of 0.3 mg/mL showed the optimal protective effect. For the ELZCP disassembled prescriptions, Liuwei-Dihuang could decrease OHC loss rate than that in the 0.3 mmol/L GM model group (P<0.05), but the OHC loss rate was still higher than that in the ELZCP group (P<0.01), which indicated that the protective effect of hair cells by Liuwei-Dihuang was not better than that of ELZCP. Poria decreased OHC loss rate from 72.1 % +/-3.7 % to 58.8 %+/- 8.2 % (P<0.05).

CONCLUSIONSELZCP could play a role in antagonizing the injury of cochlear hair cells induced by GM ototoxicity,: and its disassembled prescriptions, Liuwei-Dihuang was the main component to protect the cochlear hair cells from GM-induced ototoxicity, and Magnetitum combined with Radix Bupleurui could strengthen the action of the whole prescription; Poria could reduce GM-induced OHC loss.

Animals ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; pharmacology ; Gentamicins ; toxicity ; Hair Cells, Auditory, Inner ; drug effects ; pathology ; Hair Cells, Auditory, Outer ; drug effects ; pathology ; Mice ; Organ of Corti ; drug effects ; pathology ; Prescriptions ; Tablets

Objective: To understand the relationships between video time, exercise time and the mental sub-health of Chinese adolescents, and to assist the development of Chinese adolescents’ mental health. Methods: In this study, 16 545 adolescents aged 13-22 years in six administrative regions of China were surveyed using an adolescent sub-health multi-dimensional assessment questionnaire (MSQA), and daily physical exercise time, video screen time and other indicators were recorded. Binary Logistic regression analysis was used to understand adolescents’ mental sub-health and the correlation between video time and exercise time. Results: Detection rate of mental sub-health status in adolescents with video time ≤2 h/d was lower than that of adolescents with video time >2 h/d(19.1%，22.1%), and the detection rate of adolescents with exercise time ≤60 min/d(22.1%，17.7%) was higher than that of adolescents with exercise time >60 min/d. These differences were statistically significant (χ2=14.47, 6.97, P<0.05). Binary Logistic regression analysis showed that the risk of mental sub-health status for Chinese adolescents whose screen time was more than 2 h/d was 1.20 times that of those with screen time ≤2 h/d, and the difference was statistically significant (P<0.01). The risk of mental sub-health for students whose exercise time was > 60 min/d was 0.86 times that of students who exercised ≤ 60 min/d, and the difference was statistically significant (P<0.05). Conclusion Screen time >2 h/d and exercise time <60 min/d were negative factors leading to mental sub-health symptoms in Chinese adolescents.It is proposed to jointly promote the healthy adolescent development through health education,as well as positive family and social environment.

OBJECTIVETo study the variation of specific antibody among convalescent of severe acute respiratory syndrome (SARS) patients through a three-year program.

METHODSSera samples were collected from SARS cases in the 5th, 20th and 35th month after onset of the illness. The SARS-CoV specific antibody was detected for all of them by ELISA and neutralized test simultaneously. The titer of neutralizing antibodies was calculated using Reed-Muench method, and the comparison between different time groups was analyzed regarding the variance of data on repeated measures after logarithm conversion.

RESULTS13, 17 and 13 sera samples were collected in the 5th, 20th and 35th month after onset. Results showed that despite the fact that the positive rates of ELISA antibody were 100%, 82.4% and 84.6% respectively,the neutralizing antibody was still positive for all the samples. The average neutralizing antibody titers were 1:43 (1:16-1:203), 1:36 (1:17-1:59) and 1:21 (1:10-1:39) on the 5th, 20th and 35th month after onset, and the differences were statistically significant (F = 60.419, P < 0.001). On the 35th month after the onset, 30.8% (4/13) of the patients were still having the neutralizing antibody level of above 1:36, but the neutralizing antibody level in another 30.8% (4/13) of the patients had decreased to as low as 1:10, when the cut-off level was set as 1:8.

CONCLUSIONResults of the study indicated that the neutralizing antibody of SARS cases could last for at least three years, but the sera specific antibody in SARS cases decreased gradually when time went by. However, neutralizing antibody in some of the cases decreased to a lower level on the 35th month. Further follow-up study was worthwhile to observe the long-lasting profile of antibody existence on SARS cases.

Antibodies, Neutralizing ; analysis ; Enzyme-Linked Immunosorbent Assay ; Follow-Up Studies ; Humans ; Severe Acute Respiratory Syndrome ; immunology

OBJECTIVETo investigate the role of postoperative chemoradiotherapy (CRT) as a multimodality treatment option for locally advanced thoracic esophageal squamous cell carcinoma (ESCC) by a prospective comparison between surgery alone and postoperative CRT.

METHODSUsing preoperative computed tomography (CT)-based staging criteria, 158 patients with ESCC (stage II-III) were enrolled in this prospective study. With informed consent, the patients were randomized into two groups: postoperative CRT (78 cases) and surgery alone (S, 80 cases). After a few minor adjustments to the enrolled patients, the actual patients of postoperative CRT group and S group were 74 cases and 77 cases, respectively. Comparison of the complications, local recurrence rate, distant metastasis rate, survival rate and progression-free survival in the two groups was carried out.

RESULTSWith a median follow-up of 37.5 months, the 1-, 3-, 5-, 10-year overall survival (OS) rates were 91.0%, 62.8%, 42.3%, 24.4% and 87.5%, 51.3%, 33.8%, 12.5% for the postoperative CRT and S arm, respectively. A significant difference in OS was detected between the two arms (P = 0.0276). There was a significant difference of progression-free survival (PFS) between the two arms (P = 0.0136). The local recurrence rates in the postoperative CRT group and S group were 14.9% and 36.4%, respectively (P < 0.05). No significant difference was detected between the complications of the two groups (P > 0.05). Toxicities of chemoradiotherapy in the postoperative CRT arm were moderate, which can be relieved rapidly by adequate therapy.

CONCLUSIONRational application of postoperative chemoradiotherapy can provide a benefit in progression-free survival and overall survival in patients with locally advanced esophageal squamous cell carcinoma.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Squamous Cell ; pathology ; therapy ; Chemotherapy, Adjuvant ; Cisplatin ; administration & dosage ; Disease-Free Survival ; Esophageal Neoplasms ; pathology ; therapy ; Esophagectomy ; methods ; Female ; Follow-Up Studies ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; Prospective Studies ; Radiotherapy, Adjuvant ; Radiotherapy, High-Energy ; Survival Rate

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by the accu-mulation of immature myeloid progenitor cells in the bone marrow,compromising of normal hematopoi-esis and ultimately resulting in bone marrow failure. Chemotherapy is the mainstay treatment for all AML patients,however,drug resistance and clinical relapse limits its efficacy.The 5-year survival rate of AML patients is only 26.6%.Survival rates are even lower among patients ages 65 to 74 years (5.3%)and 75 years or older(1.6%).Therefore,exploring novel therapeutic agents is urgent for improving the outcome of patients with AML. Saponins are amphipathic glycosides found in traditional Chinese medicines. In the present study, we isolated a panel of saponins from Paris forrestii (Takht.) H. Li, a unique plant found in Tibet and Yunnan provinces, China. By examining their activities in suppressing acute myeloid leukemia cell proliferation, total saponins from Paris forrestii (TSPf) displayed more potent activity than individual ones.TSPf induced more than 40% AML cell apoptosis within 24 h and decreased the viability of all leukemia cell lines. TSPf-induced apoptosis was confirmed by both Annexin V staining and caspase-3 activation.TSPf downregulated pro-survival proteins Mcl-1,Bcl-xL and Bcl-2,but upreg-ulated the expression of tumor suppressor proteins p53,p27,Bax and Beclin 1.The AKT/mTOR signaling pathway is frequently over activated in various AML cells,and TSPf was found to suppress the activa-tion of both AKT and mTOR,but had no effects on their total protein expression.This was further con-firmed by the inactivation of 4EBP-1 and p70S6K,two typical downstream signal molecules in the AKT/mTOR pathway. More specifically, TSPf-inactivated AKT/mTOR signaling was found to be associated with downregulated RNF6, a recently identified oncogene in AML. RNF6 activated AKT/mTOR, and consistently, knockdown of RNF6 led to inactivation of the AKT/mTOR pathway. Furthermore, TSPf suppressed the growth of AML xenografts in nude mice models. Oral administration of 100 mg·kg-1 body weight almost fully suppressed tumor growth within 14 d, without gross toxicity. This study thus demonstrated that TSPf displays potent anti-AML activity by suppressing the RNF6/AKT/mTOR pathway. Given its low toxicity,TSPf could be developed for the treatment of AML.

Objective:To build the standardized knowledge base for hierarchical prevention care of neonatal hypoglycemia based on the risk prediction model of neonatal hypoglycemia, and to provide a decision-making basis for risk management to achieve predicitive neonatal hypoglycemia.Methods:Based on the best evidence summarized in strategies for the prevention and management of neonatal hypoglycemia published in 2020, evidence on the prevention and management of neonatal hypoglycemia was searched from BMJ Best Practice, UpToDate, Registered Nurses Association of Ontario, CNKI and other domestic and foreign databases and professional association websites. The retrieval period was from September 1, 2019 to August 31, 2022. The quality of newly included literature was evaluated, new evidence was extracted, and the best evidence in the prevention and management strategy of neonatal hypoglycemia published in 2020 was summarized and combined to form the first draft of the knowledge base. Experts in the field of neonatal nursing were invited to revise and discuss each item of the knowledge base, and the final draft of the knowledge base was formed. The final draft of the knowledge base was coded using the 2.5 version of the Clinical care classification system as the standardized language.Results:The risk prediction model of neonatal hypoglycemia was used as a grading tool, the final draft of the knowledge included 1 nursing diagnosis, 6 modules and 18 specific preventive nursing measures.Conclusions:The knowledge base for hierarchical prevention care of neonatal hypoglycemia based on risk prediction model can realize the prospective hierarchical nursing of neonatal hypoglycemia, which is scientific and practical, and is the basis to assist nurses to make clinical decisions.

To enhance the accuracy of computer-aided diagnosis of adolescent depression based on electroencephalogram signals, this study collected signals of 32 female adolescents (16 depressed and 16 healthy, age: 16.3 ± 1.3) with eyes colsed for 4 min in a resting state. First, based on the phase synchronization between the signals, the phase-locked value (PLV) method was used to calculate brain functional connectivity in the θ and α frequency bands, respectively. Then based on the graph theory method, the network parameters, such as strength of the weighted network, average characteristic path length, and average clustering coefficient, were calculated separately (
Adolescent ; Brain/diagnostic imaging* ; Diagnosis, Computer-Assisted ; Electroencephalography ; Female ; Humans ; Support Vector Machine

OBJECTIVE: To investigate the role of acetylated modification induced by coactivator p300 in lipopolysaccharide (LPS)- induced inflammatory mediator synthesis and its molecular mechanism. METHODS: Agilent SurePrint G3 Mouse Gene Expression V2 microarray chip and Western blotting were used to screen the molecules whose expression levels in mouse macrophages (RAW246.7) were correlated with the stimulation intensity of LPS. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (chip-qPCR) were used to verify the binding of the molecules to the promoters of IL-6 and TNF-α genes. The effects of transfection of RAW246.7 cells with overexpression or interfering plasmids on IL-6 and TNF-α synthesis were evaluated with ELISA, and the binding level of the target molecules and acetylation level of H3K27 in the promoter region of IL-6 and TNF-α genes were analyzed by chromatin immunoprecipitation sequencing technique (chip-seq). RESULTS: Gene microarray chip data and Western blotting both confirmed a strong correlation of p300 expression with the stimulation intensity of LPS. Immunocoprecipitation confirmed the binding between p300 and c-myb. The results of EMSA demonstrated that c-myb (P < 0.05), but not p300, could directly bind to the promoter region of IL-6 and TNF-α genes; p300 could bind to the promoters only in the presence of c-myb (P < 0.05). The expressions of p65, p300 and c-myb did not show interactions. Both p300 overexpression and LPS stimulation could increase the level of promoter-binding p300 and H3K27 acetylation level, thus promoting p65 binding and inflammatory gene transcription; such effects were obviously suppressed by interference of c-myb expression (P < 0.05). Interference of p65 resulted in inhibition of p65 binding to the promoters and gene transcription (P < 0.05) without affecting p300 binding or H3K27 acetylation level. CONCLUSION LPS can stimulate the synthesis of p300, whose binding to the promoter region of inflammatory genes via c-myb facilitates the cohesion of p65 by inducing H3K27 acetylation, thus promoting the expression of the inflammatory genes.
Acetylation ; Animals ; Inflammation Mediators ; Interleukin-6/metabolism* ; Lipopolysaccharides/pharmacology* ; Mice ; Tumor Necrosis Factor-alpha/metabolism*